Chronic dietary supplementation with kynurenic acid, a neuroactive metabolite of tryptophan, decreased body weight without negative influence on densitometry and mandibular bone biomechanical endurance in young rats

• Published in: PloS one Vol. 14; no. 12; p. e0226205
• Main Authors: Tomaszewska, Ewa, Muszyński, Siemowit, Kuc, Damian, Dobrowolski, Piotr, Lamorski, Krzysztof, Smolińska, Katarzyna, Donaldson, Janine, Świetlicka, Izabela, Mielnik-Błaszczak, Maria, Paluszkiewicz, Piotr, Parada-Turska, Jolanta
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 06-12-2019; Public Library of Science (PLoS)
• Subjects: Age; Amino acids; Animals; Animals, Newborn; Biology and Life Sciences; Biomechanical Phenomena - drug effects; Biomechanics; Biophysics; Body weight; Body weight gain; Bone Density - drug effects; Bone histomorphometry; Bone turnover; Bones; Breast milk; Case-Control Studies; CAT scans; Computed tomography; Densitometers; Densitometry; Diet; Dietary Supplements; Drinking water; Ecology and Environmental Sciences; Female; Fractures (Injuries); Glutamate; Glutamic acid receptors (ionotropic); Health; Health aspects; Homeostasis; Kynurenic acid; Kynurenic Acid - administration & dosage; Kynurenic Acid - pharmacology; Laboratories; Lactation; Life sciences; Male; Males; Mandible; Mandible - drug effects; Mandible - physiology; Material properties; Mechanical properties; Mechanical tests; Medicine and Health Sciences; Metabolism; Metabolites; Milk; Neonates; Nutrition; Organic acids; Osteoporosis; Physical Sciences; Physiology; Rats; Rats, Wistar; Receptors; Skeleton; Tomography; Tomography, X-Ray Computed; Tryptophan; Water; Weaning; Weight Loss - drug effects; Germany; Poland
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0226205

Kynurenic acid (KYNA) is a neuroactive metabolite of tryptophan. KYNA naturally occurs in breast milk and its content increases with lactation, indicating the role of neonatal nutrition in general growth with long-term health effects. KYNA is also an antagonist of ionotropic glutamate receptors expressed in bone cells. The aim of this study was to establish the effects of chronic KYNA supplementation on bone homeostasis in young rats, using mandible as a model bone. Female and male newborn Wistar rats were divided into control and KYNA-administered groups until 60 days of age (25x101 mg/L or 25x102 mg/L in drinking water). Hemimandibles were subjected to densitometry, computed tomography analysis and mechanical testing. Rats supplemented with KYNA at both doses showed a decrease in body weight. There were no effects of KYNA administration and mandible histomorphometry. In males, a significant quadratic effect (P < 0.001) was observed in the densitometry of the hemimandible, where BMD increased in the group supplemented with 2.5x101 mg/L of KYNA. Analysis of mechanical tests data showed that when fracture forces were corrected for bone geometry and rats body weight the improvement of bone material properties was observed in male and female rats supplemented with lower dose of KYNA. This study showed that chronic supplementation with KYNA may limit weight gain in the young, without adversely affecting the development of the skeleton.